Benign familial hematuria: genes and variants

Genes linked to Benign familial hematuria

• COL4A4: Collagen alpha-4(IV) chain

  It combines with the alpha3 and alpha5 chains to form the mature type IV collagen network of glomerular, cochlear, and ocular basement membranes. Pathogenic variants cause autosomal Alport-spectrum disease and can present with isolated persistent hematuria.

  17 disease-causing and 50 uncertain variants in COL4A4 are linked to Benign familial hematuria.

• COL4A3: Collagen alpha-3(IV) chain

  It contributes to the alpha3-alpha4-alpha5 type IV collagen network that forms the specialized basement membrane of the renal glomerulus, cochlea, and eye. Pathogenic variants cause Alport-spectrum disease and thin-basement-membrane nephropathy, with variable kidney and hearing involvement.

  17 disease-causing and 19 uncertain variants in COL4A3 are linked to Benign familial hematuria.

Known disease-causing variants in Benign familial hematuria

Which prediction tools work for Benign familial hematuria

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• REVEL: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• phyloP: 99 out of 100
• PolyPhen-2: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 97 out of 100
• CADD: 95 out of 100

Same protein, different disease

• Autosomal recessive Alport syndrome is also caused by COL4A4 variants; they fall mostly in different places as the Benign familial hematuria variants (99 disease-causing).
• Alport syndrome is also caused by COL4A4 variants; they fall mostly in different places as the Benign familial hematuria variants (57 disease-causing).
• Hematuria, benign familial is also caused by COL4A4 variants; they fall mostly in different places as the Benign familial hematuria variants (51 disease-causing).
• Autosomal dominant Alport syndrome is also caused by COL4A4 variants; they fall partly in the same places as the Benign familial hematuria variants (6 disease-causing).
• Autosomal dominant Alport syndrome is also caused by COL4A3 variants; they fall mostly in different places as the Benign familial hematuria variants (131 disease-causing).
• Alport syndrome is also caused by COL4A3 variants; they fall mostly in different places as the Benign familial hematuria variants (128 disease-causing).
• Hematuria, benign familial is also caused by COL4A3 variants; they fall mostly in different places as the Benign familial hematuria variants (59 disease-causing).
• Autosomal recessive Alport syndrome is also caused by COL4A3 variants; they fall mostly in different places as the Benign familial hematuria variants (32 disease-causing).

Diseases related to Benign familial hematuria

• Alport syndrome, also linked to COL4A3 and COL4A4
• Autosomal dominant Alport syndrome, also linked to COL4A3 and COL4A4
• Autosomal recessive Alport syndrome, also linked to COL4A3 and COL4A4
• Hematuria, benign familial, also linked to COL4A3 and COL4A4
• Nephrotic syndrome, also linked to COL4A4
• Polycystic kidney disease, also linked to COL4A4
• Kidney disorder, also linked to COL4A3
• Focal segmental glomerulosclerosis, also linked to COL4A4

Frequently asked questions

Which genes are linked to Benign familial hematuria?

In CATVariant, Benign familial hematuria is linked to 2 analyzed proteins: COL4A4 (Collagen alpha-4(IV) chain) and COL4A3 (Collagen alpha-3(IV) chain).

How many genetic variants are linked to Benign familial hematuria?

107 variants: 34 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 69 are of uncertain significance or have conflicting reports.

Which uncertain variants in Benign familial hematuria look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Benign familial hematuria?

Among tools not trained on clinical labels, phyloP separates this disease's known disease-causing variants from harmless ones best (AUROC 0.99, based on 17 disease-causing and 96 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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